More Diabetes Answers

Why is NOT being an "early adopter" uncomfortable but might be a good thing?

You have probably seen lots of adverts on TV for new drugs to help improve your sex life, lower your cholesterol, allow you to eat salty, spicy, food without heartburn, and generally make your life better.  The adverts often show everyone looking happy and have actors dressed as earnest, sincere doctors in white coats advising you in reassuring tones that you should, "Ask you doctor about fill-in-the-blank." Then at the very end of the advert in an incomprehensibly fast rush a different voice blurts out all the fine print (including side effects, or the fact that a new fat-lowering drug actually hasn't been shown to prevent heart attacks and strokes and might in fact increase your risk of stomach bleeding... check out the website at www.lovaza.com ) 

What's a person to do when the main message is that more is better and than anything new is most likely a huge scientific advance forward and therefore a good thing.

But often it takes years before we really know if a new therapy will actually improve real health outcomes that matter to people.  There have been many examples of drugs that seemed like they were doing good but ended up causing more harm than good.  Back in the 1970s and 1980s there was a big push to give people drugs to stop the heart developing irregular rythmns after a heart attack.  Seemed like a no-brainer.  If you've just had a heart attack you wouldn't want your heart to suddenly go into irregular rythmns.  And these drugs (like encainide and flecainide) did work to make the electrical tracings of the heart (the ECGs or EKGs) look better.  But unfortunately when researchers looked at the outcomes in patients who received the new "miracle" drugs more of them died than patients who did not receive the drug.  Sometimes a drug that helped lower blood pressure (like short-acting nifedipine) can actually increase the risk of heart attacks or stroke.  Sometimes pain killers (like Vioxx) that appear to be better because they cause less risk of stomach bleeding can actually cause an increase in heart attacks.

As I have talked about in other blog postings the story with the thiazolidinediones is another example of a class of drugs that looked promising but may be causing more harm than good.  We won't know for sure for another few years.

I work for a health care organization (Group Health in Washington State) that holds itself to a very high standard.  Before we add any drug to our formulary so that our patients can get it we try to wait until there are long-term studies that show clearly that the drug is beneficial.  When those studies are published we move very fast to contact all of our patients who might benefit and offer them the drug.  But it also means that when a new drug is being hyped up by the drug companies but before we truly know if it will be beneficial we do NOT add it to our formulary.  For patients (and some of our doctors) who buy-in to the hype I often have to deal with some unhappy and angry phonecalls.  It often feels uncomfortable to be cautious and conservative.  We take a lot of heat for not being out front with "cutting edge" drugs. 

But despite the discomfort of fielding angry phone calls in the early years of new drugs, I take comfort in this.  We never had Vioxx on our formulary at Group Health.  We never had Rezulin or Avandia or Actos on our formulary either.  I don't know how many hundreds of patients are alive today because of our cautious approach because they did not get heart attacks or die as a result of taking these drugs but it does probably run into the hundreds at least.

Again, let me be clear:  I have nothing against the company who makes Lovaza and I don't know whether it will turn out to cause more good than harm.  I hope it will.  But none of will know that until larger long-term trials are done.  We do know that it causes significant side effects.  Once we know for sure that the benefits outweigh the risk we will jump on it and prescribe it widely.  But not until then.

What will history say about the thiazolidinedione class of diabetes drugs like Avandia and Actos?

Every time I hear another piece of bad news about rosiglitazone (Avandia) or pioglitazone (Actos) I feel as though I am watching another piece of diseased flesh falling off a bloated and dying giant.  The thiazolidinediones (or TZDs or glitazones) was the juggernaut new "blockbuster" diabetes drug class of the past ten years.  Despite having no research studies showing long term benefit these drugs were pushed very persuasively onto the market.  But as I have detailed in previous posts the longer we looked the longer the list of problems and side effects grew while the evidence of meaningful benefit remained elusive.

http://gomeworld.typepad.com/morediabetesanswers/2010/06/why-would-you-ever-want-to-use-avandia-or-even-actos.html

This weeks brings more bad news.  The FDA has issued a warning that pioglitazone (Actos) may cause an increased risk of bladder cancer, especially with prolonged use of the drug.  We already know that the risk of developing bone-thinning (osteoporosis) with these drugs gets worse the longer you stay on them.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226257.htm

Another announcement today states that rosiglitazone (Avandia) is being taken off the market in Europe because of the likely increased risk of heart attacks, strokes and deaths associated with taking Avandia.  Avandia will, of course, still be available in the USA market.  Although sales in the USA are dropping Avandia still brings in annual revenue of over a billion dollars.

http://link.email.washingtonpost.com/r/BZYGW4/A7M5IB/30Y38H/VMINCB/Q0A68/E4/h

Why is it that the USA seems so much slower to act as Europe just did?  This is eerily reminiscent of the situation back in 1997 when troglitazone (Rezulin), the first drug in this class, was taken off the market in the UK with most of Europe quickly following suit, but was left on the US market for another full two years before the rising toll of deaths from liver failure convinced the FDA to remove it.  I wonder how long we will need to wait before we see the last of Avandia in the USA.

I do not write this with pleasure or malice.  I have nothing against pharmaceutical companies that work to develop new treatments that might benefit people with diabetes.  Far from it.  I applaud their efforts.  In the past few decades some other classes of drugs (like ACE-inhibitors and statins) have been proven over time to be dramatically beneficial for people with diabetes.  What concerns me is how easily fooled many doctors and patients are, and how readily we all want to believe the early hype about new drugs.  How impatient we all are.  We are rarely willing to do the rigorous long-term trials that can truly prevent us from allowing millions of people to be exposed for years to drugs that cause more harm than good.